Histamine (HA), a stimulator of H, and H 2 receptors, produced dose-dependent inhibition of the melanin dispersion which normally occurs when fiddler crabs, Uca pugilator, are transferred from a white to a black background. The HA precursor L-histidine, and 4-methyl histamine (4-MeHA), an H 2 receptor agonist, also inhibited melanin dispersion. 2-Methyl histamine (2-MeHA), an H, receptor agonist, enhanced melanin dispersion. The inhibitory effects of HA and 4-MeHA were abolished by the H 2 receptor blocker metiamide but not by blockers of either H, receptors or alpha, adrenoceptors. Melanin-dispersing hormone (MDH) release is accomplished mainly by stimulation of alpha, adrenoceptors with norepinephrine appearing to be the neurotransmitter involved. The H, receptor blockers pyrilamine and SA-97 antagonized 2-MeHA. HA-induced inhibition of melanin dispersion was potentiated by the noradrenergic neuron blocker bretylium and the alpha 2 adrenoceptor agonist B-HT 933. HA did not significantly affect melanin dispersion in crabs pretreated with 6-hydroxydopamine which destroys catecholaminergic neuroterminals. None of these drugs affected the melanophores directly. On the basis of these and previously obtained results it is suggested that H, and H 2 receptors are present on norepinephrine neurons involved in triggering MDH secretion, and administered HA inhibits MDH release by decreasing impulse-mediated noradrenergic neurotransmission through stimulation of H 2 receptors.